Myeloperoxidase is a heme-containing enzyme found principally in the mammalian neutrophil. It catalyses the oxidation of chloride ion to hypochlorite which through its chlorinating action serves to kill phagocytised bacteria, fungi, viruses and possibly cancer cells. More recently the enzyme has been suggested to play a role in modulating the inflammatory response through impairment of receptor-mediated recognition mechanisms of phagocytic cells. Methionine oxidation brought about by the myeloperoxidase-H2O2-Cl- system inactivates human alpha-1-proteinase inhibitor and hence can aggravate proteolytic destruction of lung tissue in cases of emphysema. Myeloperoxidase consists of two large (57,000 MW) polypeptides, two small (10,500 MW) polypeptides, 3% to 4% by weight unidentified carbohydrate and two hemes which are thought to be iron chlorins. The two large subunits have been shown to be linked through a disulfide bridge in the case of human myeloperoxidase and these subunits also bind the chlorins which may or may not be equivalent. We have obtained three different crystal forms of canine myeloperoxidase by precipitation with methylpentanediol, polyethylene glycol or ammonium sulfate. A trigonal crystal form from ammonium sulfate precipitation diffracts X-rays strongly to Bragg spacings of less than 2 A and has a single molecule of myeloperoxidase in the asymmetric unit. This proposal is concerned with determination of the high-resolution crystal structure of canine myeloperoxidase using this crystal form. The results of this work are expected to yield new information on the organization of subunits, mode of iron chlorin binding to the protein and site of chloride substrate binding to the enzyme. It is expected that these results will help in understanding the mechanism of catalysis in this enzyme which contains unusual chromophores and may have an uncommon mode of subunit association.